X-ray fluorescence (XRF) is the most precise method of measuring body and organ burdens of heavy metals in vivo. However, the required precision for screening of chronically, low-level exposed populations for these metals, in particular lead and mercury, is between 5 and 20 times greater than achievable by current methods. This proposal describes an innovative variation of XRF which can provide an improvement in precision of one to two orders of magnitude over present technology. This is achieved by reducing the background under the signal by a factor of 10 million, while reducing the signal itself by only 100. Phase I will prove the feasibility of the approach. Three to four million young children from all levels of society are exposed to environmental sources of lead at concentrations that place them at risk of adverse health effects. The investigation of mercury is ubiquitous since many foods, and especially seafoods, contain significant amounts of mercury. There are over 100 independent occupations with possible exposures to lead or mercury. Yet, there is no tool available to measure body or organ burdens of lead or mercury with sufficient precision for screening chronically, low-level exposed populations. The proposed approach will enable the development of such a tool.